it is a presentation on different modifications of histone proteins and their effects on

1. Anilkumar C
PALM 3001

2. Histone Proteins and Genome
Imprinting

3. Now……..
1 • Histone proteins
2 • Classes of Histones
3 • Functions of histone proteins
4 • Histone modifications
5 • Genomic imprinting
6 • Mechanisms of imprinting
7 • Imprinting in plants

4. Introduction
Histone proteins: Histones are a special group of
proteins found in the nuclei of eukaryotic cells
responsible for DNA folding and chromatin
formation.

5. Chemically they are-
• highly alkaline basic proteins
• Histones are positively charged
• abundance of positive amino-acids, arginine and lysine

6. Classes of Histones:
• There are two main classes of Histones:
• Core Histones
• Linker Histones
Core Histones:
In core histones following families are included
• H2A
• H2B
• H3
• H4
• Two of each of these core histone proteins assembles to
form one octameric nucleosome core particle, and 147 base
pairs of DNA wrap around this core particle.
contain more lysine
contain more arginine

7. Linker Histones:
Linker histone included:
• H1
• H5
• The linker histone protein H1 binds the nucleosome at
the starting and ending sites of the DNA, thus locking
the DNA into place and help in the formation of higher
order structure.
• H5 histiones are individual proteins involve in the
packaging of specific region of DNA.
highest lysine/arginine ratio

8. Function of the histone protein in a
chromosome
• The DNA is housed in chromosomes in the form of
nucleosomes
• It is basic unit of chromosome or chromatin fiber. It is DNA
duplex coiled around a core of eight histone proteins
• Positively charged histones are linked with negative charged
phosphate groups of DNA

9. Levels of chromatin structure

10. • Some histone proteins function as spools for the thread-like
DNA to wrap around
• looks like beads on a string

11. • The nucleosomes + H1 histones = 30 nm spiral
Solenoid
• it maintains the chromosomal
structure

13. Histone Modifications
• Each histone protein has a structured domain, ‘Histone
Fold’ and unstructured ‘N- terminal tail’

14. Modifications…
• Acetylation
– Acetyl functional group
• Methylation
– Methyle group
• Phosphorylation
• It has been proposed that these modifications result in a
‘code’ which can be read by proteins involved in gene
expression and other DNA translations

15. Histone Acetylation & Deacetylation
• Histone acetylation
• – Histone acetyl transferases (HATs)
• Adds acetyl groups to histone tails
• Reduces positive charge and weakens interaction of histones
with DNA
• Facilitates transcription by making DNA more accessible to
RNA polymerase II
• Histone deacetylation
• – Histone deacetylases (HDACs)
• Removes acetyl groups from histone tails
• Increases interaction of
DNA and histones
• Represses transcription

16. Acetylation
• It is the introduction of an Acetyl functional group to the
Lysine amino acid of the histone tail.
• These reactions are catalyzed by enzymes with "histone
acetyltransferase" (HAT) or "histone deacetylase"
(HDAC) activity.

17. Effects of Acetylation
• -ve charge on histone
• reduces affinity of tail for adjacent nucleosomes
• creating a transcription permissive environment
• increase the access of transcription factors

18. Methylation
• It is the introduction of an Methyl functional group to
Lysine or Arginine of the histone tail.
• These reactions are catalyzed by enzymes with "histone
methyltransferase”
• ‘Arg’ can be methylated once or twice, and ‘Lys’ once,
twice of thrice.

19. Histone Methylation
• Histone methylation
• Histone methyl transferases (HMTs)
– Histone lysine methyl transferases(HKMTs)
Methylate lys (k) residues
• Protein argenin methyl transferase (PRMTs)
Methylate arge(R) residues
• Methylation can result in activation or repression of expression
 trimethylation of histone H3 at lysine 4 (H3K4) is an active mark
for transcription
 dimethylation of histone H3 at lysine 9 (H3K9), a signal for
transcriptional silencing

20. Effects of methylation
• Methylation does not neutralize charge but recruit silencing
or regulatory proteins that bind methylated histones.
• Chromodomain containing proteins interact with methylated
histone tails.
• transcription repression

21. Genomic imprinting
• The differential expression of genetic material, at either
chromosomal or allelic level, depending on whether the
genetic material has come from the male or female
parent
• Genomic imprinting is an epigenetic process
• genomic imprinting alters gene expression without altering
DNA sequence

22. • The first description of the imprinting phenomenon was
given by McGrath and Solter in 1984
• An epigenetic form of gene regulation that results in only
the copy inherited from father or mother to function
• Epigenetic modifiers of gene expression such as DNA
methylation, histone modification, non-RNA and higher-
order chromatin formation

23. Mechanisms of Imprinting
DNA Methylation
 Attachment of methyl (-CH3) groups to the bases of DNA.
 Occurs at cytosine that follows guanine at CpG dinucleotides

24. Non-coding RNAs
 A significant number of imprinted genes are transcribed
to give a non-coding RNA.
 Non-coding RNAs include antisense transcript, small
nucleolar RNAs (Sno RNAs), micro RNAs, pseudo
genes and other RNA of unknown function

25. Histone modification & chromatin
remodeling
 Histone modifiations includes Acacetylation of lysines
(HATs), Phosphorylation of serines (Kinases) and
Methylation of lysines
 Methylation of lysine-4 in H3 is associated with active
genes and methylation of lysine-9 in H3 is associated with
inactive genes
 The allele-specific gene silencing in H19 is in part
mediated by hypermethylation and histone deacetylation

26. Imprinted genes in plants
• A similar imprinting phenomenon has also been described
in flowering plants (angiosperms)
• imprinted genes are responsible for the triploid block effect
in flowering plants that prevents hybridization between
diploids and autotetraploids.

29. Conclusion
• Histone proteins are most important for packaging and
ordering of DNA
• Modifications to histone proteins as a mechanism of
genome imprinting cause epigenetic changes in the
expression of phenotype
• But they do not alter the genetic constitution